Wound Infection: From the Bench to Bedside and Back

Bacteria and other infectious organisms play a varied role in wound healing. Complicating acute wound healing by prolonging the inflammatory phase of healing, infectious organisms may cause a variety of wounds from epidermal loss associated with impetigo (Staphylococcus) and cold sores (herpes simplex), as well as deeper wounds causing ecthyma (Pseudomonas) or necrotizing fasciitis (aerobic or anaerobic bacteria).^1–5 In some cases of non life-threatening infections, the host response to the infection, rather than the infectious organism itself, is primarily responsible for the associated morbidity.⁶ Interestingly, these same disease-causing organisms, such as herpes simplex, are now being used as instruments to treat diseases, such as cancer.⁷

Bacteria in chronic wounds present an even more complicated picture. For example, most chronic wounds heal in the presence of multiple bacteria. It has even been suggested that the increase in the growth of bacteria under an occlusive dressing of rapidly healing, partial-thickness wounds are not solely non-pathogenic but causal in faster healing. Alternatively, infection is the major event that leads to amputation for a patient with a diabetic foot ulcer.⁸ Therefore, it has long been hypothesized that bacteria in healing compared to non-healing wounds differ by the type or the amount of bacteria. Interestingly, some data suggest that the number of bacteria might be a consequence of underlying pathology and a result of non-healing status, as opposed to the cause of non-healing.⁹ More recently, it has been hypothesized that the way bacteria reside in the wound might be important, either in the planktonic or free-floating state, or as a colony in a biofilm.¹⁰ A local or systemic steady state might also exist between the wound and the organisms, which will impede healing, and if disrupted may result in more severe complications, such as sepsis.

This issue of WOUNDS presents a spectrum of articles that focus on infection (much like the spectrum of roles bacteria play in wounds) ranging from the use of novel animal models for infection, to an unusual case report of uncommon infection, to correlating bacterial sampling techniques, to a new way to treat bacteria and maintain the sterility of wound dressings.

Salehifar and colleagues tackle the question of the utility of swab cultures in burn patients. Perhaps no other group is at such high risk from the severe consequences of infection than those who suffer from burns. Studying a cohort of 39 patients with severe and less severe burns, they studied 156 samples (half tissue and half swab samples) taken at day 7 and 14. Interestingly, P aeruginosa and C freundii were the two microorganisms found most often by both sampling methods. The rate of concordance between swab and the standard of care, a tissue biopsy (eg, both sample negative and both sample positive with the same microorganism) was 87.1% and 66.6% at days 7 and 14, respectively, suggesting the potential of swab cultures to direct antibiotic therapy especially at the earlier time period.

Patients with burns are not unique in their susceptibility to infection. Other groups immunosuppressed by other mechanisms are also at significant risk. To better understand these patients, Geerings et al report on the development of a novel wound model to study infection. Designing a surgical implantable chamber that is placed in a mouse, these investigators were able to study the relative role of immunosuppression on the progression of wound infection. A 4-piece chamber was implanted in healthy, chemotherapy-treated mice, and then a bacterial load was placed inside the chamber. While healthy mice developed a significant inflammatory response to the bacteria, the bacteria remained localized to the skin and soft tissue. This was in contrast to Pseudomonas inoculation within the chamber in mice treated with cyclophosphamide. This group of mice succumbed to the infection; Pseudomonas was cultured from those mice livers and spleens.

For what many believe are obvious reasons, reducing bacterial counts in the wound and preventing the spread of infection by keeping bacteria out of dressings is important. Based on that premise, De Smet et al studied the Glucose oxidase-Lactoperoxidase-Guaiacol (GLG) enzyme system as a potential therapy for treating bacteria in wounds and dressings. Taking advantage of the knowledge regarding natural oxidase-peroxidase system to treat infection, the GLG-enzyme system was evaluated in its ability to control and kill bacteria without host cytoxicity. The GLG system was quite effective in controlling bacteria as determined by the Minimal Inhibitory Concentrations (MIC90) and had a nearly equal ability to kill bacteria (Minimal Bactericidal Concentration [MBC]) without significant cytotoxicity. MRSA appeared particularly susceptible; unfortunately, 2 refractory strains, E coli and Pseudomonas, were also resistant to the GLG-enzyme system.

While these laboratory and translational studies help advance the knowledge of infection and wound care, Eggert et al reminds of us how devastating and insidious bacterial infections can be. They present a healthy 14-year-old girl who, after seemingly minor trauma several days before, developed swelling and purpura of her arm as the first manifestation of necrotizing fasciitis. Rapid and aggressive treatment salvaged function and cosmetic appearance in what was a dramatic infection. The treatment required extensive debridement and significant adjuvant care.

Infection persists as our wound healing nemesis, and much remains to be learned. This issue highlights some important basic and clinical advances, and serves as a dramatic reminder of the consequences of severe infections. While this issue is a welcomed addition to the literature, continued thought, observation, study, and close scrutiny of infection-related issues is necessary.

From the Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida

Address correspondence to:
Robert S. Kirsner, MD, PhD
PO Box 016250 (R250)
Department of Dermatology
University of Miami Miller School of Medicine
Miami, FL 33136
rkirsner@med.miami.edu